Von Willebrand disease is a common diagnosis in the USA. In some cases the disorder is under-diagnosed, particularly in adult females with menorrhagia. In other situations, VWD may be over-diagnosed based on less precise laboratory testing at the time of diagnosis, incorrect interpretation of the lab results at diagnosis, the lab testing was abnormal but the patient had no clinical bleeding correlate, or the field has changed concerning the stringency of diagnostic criteria (NHLBI Guidelines). Aim 1 of this project will continue the ongoing study of type 1 (and other VWD types) to clarify the stringency of VWD diagnosis and provide a suggested approach to substantiating, questioning, or removing the diagnosis of VWD. Aim 2 will develop improved alternative assays for VWF function. Currently the only widely utilized test of VWF function is the ristocetin co-factor assay (VWF:RCo). There are widely recognized problems with sensitivity, specificity, and clinical correlation of that assay - in part do to the interaction between ristocetin and the test VWF. Aim 3 will continue to determine the genotype - phenotype correlation of VWF alteration by determining VWF sequence variations based on race or ethnicity within the US population. Aim 4 will carry out clinical projects that are currently being piloted at single centers (menorrhagia at Milwaukee and QOL Studies at Indiana). Not only is this study population important to the studies proposed in Aim 1, but this cohort is also critical to the studies proposed in Project 2 and Project 3. This careful clinical and laboratory phenotyping in this project will not only improve the fidelity of VWD diagnosis, but it will begin the pathway of how to approach individuals with a prior diagnosis of VWD that might have neither abnormal laboratory testing nor a current abnormal clinical bleeding risk.